A correlation of endocrine and anticancer effects of some antagonists of GHRH

Magdolna Kovács, Andrew V. Schally, Florian Hohla, Ferenc G. Rick, Éva Pozsgai, Luca Szalontay, József L. Varga, Márta Zarándi

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

GHRH receptor antagonists inhibit growth and metastasis of a large number of experimental tumors expressing the pituitary GHRH receptor (pGHRH-R) and its major splice variant SV1. In this study, using Western blot, we demonstrated that DBTRG-05 and U-87MG human glioblastoma cell lines express pGHRH-R at levels 6-15 times higher than SV1. To reveal a correlation between the anticancer activity and the endocrine potency on inhibition of GH release, we compared the antitumor effect of GHRH antagonists JV-1-63 and MZJ-7-138 on growth of DBTRG-05 human glioblastomas grafted into athymic nude mice with their inhibitory potency on GH release. JV-1-63 strongly suppressed the stimulated GH secretion induced by clonidine in rats and inhibited the exogenous GHRH-induced GH surge by 88-99% in vivo and in vitro. MZJ-7-138 decreased the stimulated GH secretion by 58% in vitro and showed only a tendency to inhibit GH secretion in vivo. The strong inhibitor of GH release JV-1-63 reduced tumor growth of DBTRG-05 glioblastomas in nude mice by 46%, while the weak GH release suppressor MZJ-7-138 did not have an effect. Exposure of DBTRG-05 cells to the GHRH antagonists in vitro caused an upregulation of mRNA expression for pGHRH-R and a downregulation of SV1 expression, with JV-1-63 having significantly greater effects than MZJ-7-138. Our results demonstrate that a positive correlation exists between the endocrine potency and the antiproliferative efficacy of GHRH antagonists in tumors strongly expressing pGHRH-R.

Original languageEnglish (US)
Pages (from-to)1839-1846
Number of pages8
JournalPeptides
Volume31
Issue number10
DOIs
StatePublished - Oct 1 2010

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Keywords

  • Anticancer
  • GH
  • GHRH antagonist
  • GHRH receptor
  • Glioblastoma
  • mRNA

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

Kovács, M., Schally, A. V., Hohla, F., Rick, F. G., Pozsgai, É., Szalontay, L., Varga, J. L., & Zarándi, M. (2010). A correlation of endocrine and anticancer effects of some antagonists of GHRH. Peptides, 31(10), 1839-1846. https://doi.org/10.1016/j.peptides.2010.07.006